The goal of this proposal is to prepare new cyclic polynuclear and supramolecular metal complexes that have the potential for being unusual drug transport and/or molecular recognition systems for biologically important molecules. This is a form of host-guest chemistry. The cyclic polynuclear complexes alone are expected to have biomedical applications as well due to the known therapeutic behavior of the specific metals that they contain. The systems will have potential value in the treatment of diseases, such as cancer, arthritis, or HIV. The polynuclear complexes will be composed of a transition metal, such as palladium(ll), platinum(ll), or gold(Ill), a bidentate chelating ligand, and a bridging ligand containing two strategically located nitrogen atoms as binding sites. The bridging ligands will be biologically active molecules themselves, either therapeutic molecules or molecules that are naturally found in biological systems, such as purine nucleosides and nucleotides, including several known drugs. Molecules to be tested for molecular recognition will be aromatic compounds and hydrophobic molecules. These will interact with the supramolecular complex via non-covalent forces, such as pi-pi, hydrophobic or hydrogen bonding. Molecules to be tested include amino acids, carboxylic acids, and aromatic and aliphatic compounds. The specific aims are (1) to synthesize and characterize the polynuclear complexes; (2) to investigate the molecular recognition properties of various kinds of cyclic polynuclear hosts; (3) to measure the stability constants for the binding of the host-guest complexes to screen for potentially useful systems; (4) to encapsulate the hosts and/or host-guest complexes in liposomes to examine their potential as drug delivery systems. In particular, the liposome systems of Pd(ll) and Pt(ll) and their host-guest complexes in which the guest is a known antitumor drug, such as altetramide or flutamide, will be investigated. This methodology has the potential for developing new therapies for treating cancer, particularly multidrug resistant tumors.